Sealed sources of Am-241 emit primarily 60 keV photons; produce relative dose distributions in water comparable to those from Cs- 137 or Ra-226 sources; and can produce dose rates up to 100 cG/hr at 1 cm in water. Am-241 gamma rays can be shielded effectively by thin layers of high atomic number materials (HVL in 1/8th of lead) placed on the applicator or inside some body cavities (for example, hypaque in bladder, barium sulphate in rectum). These properties of Am-241 sources open a new approach to optimizing intracavitary irradiation of various cancers by allowing a reduction in dose to and volume of irradiated critical organs or by increasing tumor doses. The relative ease with which highly effective shielding is achievable with Am-241 sources would allow the design and fabrication of partially shielded applicators which can produce asymmetric dose distributions to allow undirectional irradiation of localized lesions and would reduce the radiation exposure to personnel. This proposal seeks to continue an ongoing investigation into physical, biological and clinical aspects of intracavitary irradiation using Am-241 sources. The current first-generation gynecological applicator will be modified to produce a second- generation Am-241 applicator for treatment of primary gynecological cancers. Am-241 sources and clinical applicators for intracavitary irradiation of other disease sites such as rectum, esophagus, etc., will be developed. Dose distributions produced by these applicators will be measured using ionization chambers and thermoluminiscent dosimeters in tissue equivalent phantoms. An existing dose computation model will be extended to include the effects of partial shields on the applicators and source-to-source shielding on the primary and scattered photons using a 3- dimensional scatter-integration model. Relative biological effectiveness (RBE) of Am-241 photons as compared with Ir-192 and I-125 photons will be determined in a rat solid tumor system for dose rates in the range of 10 to 100 cG/hr using tumor cell survival and tumor cure as the endpoint. The potential benefit for brachytherapy provided by partial shielding of a critical organ, for example, part of the circumference of the rectum, will be assessed by studying the early and late radiation response of partially irradiated rodent intestine. Ongoing clinical trials for recurrent gynecological cancers using Am-241 applicators will be continued and clinical studies for intracavitary irradiation of primary gynecological cancers and recurrent cancers of the rectum, esophagus, anus, head and neck, and skin using Am-241 sources will be conducted.